The object of our proposed research is to gain a better understanding of the genetic and molecular basis of bacterial-host cell interactions. We focus on three aspects of this association: the entry of bacteria (Yersinia and Salmonella) into cultured epithelial cells and macrophages; the analysis of the intercellular and transcytotic pathways followed by these invasive bacteria in well-defined cell culture models; and the interactions of these bacteria in the M cells and Peyer's patches of susceptible and resistant animals. We continue to investigate the genetic and molecular determinants of pathogenicity that permit these microbes to enter cells or to prevent their destruction by cellular and humoral host factors. Our preliminary work in these areas has been most encouraging and suggests that these aspects of microbial pathogenesis are amenable to fruitful experimental investigation.